neoadjuvant dasatinib and radical cystectomy for transitional cell carcinoma of the bladder

Conditions: Transitional Cell Carcinoma of the Bladder

Summary: this pilot study is designed to determine feasibility and safety of treatment with dasatinib administered orally once daily for 4 weeks duration prior to radical cystectomy for urothelial carcinoma of the bladder.

outline: this is a multi-center study. this is a pilot study designed to determine the safety and feasibility of treatment with dasatinib 100 mg administered orally once daily for 4 weeks duration prior to radical cystectomy for patients with muscle-invasive transitional cell carcinoma of the bladder ineligible for and/or willing to forgo neoadjuvant cisplatin-based combination chemotherapy. if surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery. ecog performance status 0-1 life expectancy: not specified hematopoietic: * absolute neutrophil count (anc) \> 1.5 k/mm3 * platelets \> 100 k/mm3 * inr \< 1.2 hepatic: * total bilirubin \< 2.0 x upper limit of normal (uln) * aspartate aminotransferase (ast) ≤ 2.5 x uln. * alanine aminotransferase (alt ) ≤ 2.5 x uln renal: * serum creatinine \< 2 x uln cardiovascular: * no uncontrolled angina, congestive heart failure or mi within 6 months prior to registration on study. * no diagnosed congenital long qt syndrome (a congenital disorder characterized by a prolongation of the qt interval on ecg and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death). * no history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes). * no prolonged qtc interval on pre-entry electrocardiogram (\> 450 msec), obtained within 28 days prior to being registered on study.

Eligibility criteria:
inclusion criteria: * histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage ii-iva) with no evidence of metastatic disease (focal squamous and/or adenocarcinoma differentiation defined as ≤ 10% of tumor volume allowed, sarcomatoid and small-cell components not allowed). patient with any degree of fixation of the pelvic sidewall are not eligible. * patients must be willing to undergo a cystoscopy, prior to registration on study if tumor block is not available. * eligible for radical cystectomy as per the attending urologist. * all patients must be willing to forego neoadjuvant cisplatin-based combination chemotherapy and understand it is an option post-surgery or must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist. * prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder. * written informed consent and hipaa authorization for release of personal health information. * age \> 18 years at the time of consent. * females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. * females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. * females must not be breastfeeding. * ability to take oral medication (dasatinib must be swallowed whole). exclusion criteria: * no prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, gleason \< grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 5 years. * no treatment with any investigational agent within 30 days prior to being registered for protocol therapy. * no prior systemic chemotherapy for transitional cell carcinoma of the bladder( prior intravesical therapy is allowed). any other prior chemotherapy must have been completed \> 5 years prior to initiation of therapy. * following concomitant medications must be discontinued 7 days prior to registration on study and for the duration of dasatinib therapy: bisphosphonates - due to risk of hypocalcemia; drugs that are generally accepted to have a risk of causing torsades de pointes; any prohibited cyp3a4 inhibitors/inducers/substrates; anti-coagulation and/or anti-platelet therapies to avoid potential bleeding risks. * no clinically significant infections as judged by the treating investigator. * no pleural or pericardial effusion of any grade. * history of diagnosed congenital bleeding disorders (e.g., von willebrand's disease) * no history of diagnosed acquired bleeding disorder (e.g., acquired anti-factor viii antibodies) within one year prior to registration on protocol therapy. * no history of ongoing or recent (within \<3 months prior to registration on protocol therapy) significant gastrointestinal bleeding. * no known history of hypokalemia that cannot be corrected prior to registration on protocol therapy. * no known history of hypomagnesemia that cannot be corrected prior to registration on protocol therapy.